Coronary heart disease (CHD) is the leading cause of death in women. Observational studies suggest that postmenopausal estrogen replacement therapy (ERT) reduces the risk of new CHD events by 50% in healthy women, and by 80% in women with prior CHD. The mechanism of the apparent cardioprotective effect is unclear but could include inhibition of the pathogenesis and progression of atherosclerosis through favorable changes in serum lipids, or protection against thrombosis and infarction through favorable changes in vascular and platelet mediators. To clarify the possible mechanism of a cardioprotective effect of ERT, we propose to conduct a clinical trial as an ancillary component to the Hormone Replacement Study (HRS) (a multicenter clinical trial of ERT for prevention of cardiovascular mortality). At least one hundred and fifty- six (156) of the Bowman Gray HRS participants will undergo coronary arteriography at baseline and after three years of treatment. In addition, all of the HRS participants enrolled at Bowman Gray will undergo baseline and annual follow-up B-mode ultrasound of the carotid arteries. The primary outcomes, progression or regression of coronary atherosclerosis measured by quantitative coronary angiography, and of carotid atherosclerosis measured by quantitative B-mode ultrasound of the carotid arteries, offer powerful tools to detect differences in progression or regression of atherosclerosis between either hormone group compared to placebo. The trial will also examine the relationship between ERT associated changes in lipids and progression or regression of coronary and carotid atherosclerosis, and correlate changes in coronary and carotid disease. The effect of ERT and PERT on progression of coronary and carotid artery disease will add important complementary data to the clinical outcomes measured in the HRS trial and help determine the mechanisms of any observed benefit of ERT or PERT on cardiovascular mortality. In addition, it will provide more precise information about the degree to which carotid atherosclerosis is an accurate reflection of the extent of coronary atherosclerosis.